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Both of you are discussing alcohol research. I do not know whether you wish to be combined for a little extra time.

Dr. VAN THIEL. That would be fine.

Senator ADAMS. Dr. Perrine, do you wish to come forward and participate in this or not? We would be very pleased to have you. As I say, we are on the same subject, so we might be able to get a little broader perspective this way.

Welcome, all of you.

Also, Dr. Perrine, Senator Leahy wanted to say he was sorry that he could not be here this morning to specifically greet you. He sends his regrets for that, but we hope he is off doing good work. in the Senate.

Please, gentlemen, proceed.

Dr. VAN THIEL. Senator Adams, members and staff of the subcommittee, thank you for the opportunity to appear before you today and to present testimony concerning the issues of alcohol abuse, alcohol research, and its funding. My name is David Van Thiel, I am the current president of the Research Society on Alcoholism. I am also the scientific codirector of the Alcohol Research Center at the University of Pittsburgh School of Medicine. Finally, I am the medical director of the transplant program at the University of Pittsburgh.

As the president of the Research Society on Alcoholism, I represent the large body of basic scientists and social scientists who are investigating means to identify and treat alcohol abusers and alcoholics as well as to prevent both of these important problems.

As a scientific codirector of the Alcohol Research Center at the University of Pittsburgh, I am actively involved in directing, coordinating and performing alcohol-related research that relates to the problem of adolescent alcohol abuse.

Specifically, the Alcohol Research Center is interested in the physical and psychosocial maturational changes that occur in adolescence and contribute to the initiation and perpetuation of abnormal use or abuse of alcoholic beverages by the unique population of individuals between the ages of 10 and 16 years of age. It must be obvious to you as it is to us in Pittsburgh that any attempt to modify the use and acceptance of alcoholic beverages by adolescents may have profound effects upon their physical and psychosocial development as well as upon their continued use of alcoholic beverages.

In this regard, it is important to note that suicide and accidental death are the two major causes of death among adolescents and that alcohol abuse is estimated to be involved in 30 percent of all suicides and accidental deaths in the general population. The rates for both of these problems in adolescence are probably considerably greater.

In 1989 motor vehicle injuries accounted for more than 45,000 deaths, of which one-half were alcohol related. Alcohol-related traffic fatalities are the No. 1 cause of adolescent death. Nearly 4 percent of college students or nearly one-half million young adults drink alcohol daily. Worse yet, when surveyed, currently more than two-thirds of these individuals do not appreciate the risks associated with excessive alcohol use.

At the level of spending, it is estimated that $4.2 billion is spent each year by college students on alcoholic beverages. Shamefully, less money is spent annually by college libraries and on scholarships or fellowships throughout the United States on an annual basis.

As for our society at large, it should be noted that 49 percent of all murders, 68 percent of all manslaughters, 52 percent of all rapes and sexual assaults, 48 percent of all robberies, 62 percent of assaults, and 49 percent of violent crimes are perpetrated by individuals who are under the influence of alcohol. Many of these are adolescents and young adults.

As the medical director of the transplant program at the University of Pittsburgh, I am aware of the fact that alcohol-related cirrhosis is the ninth leading cause of death among young adults and accounts for greater than 28,000 lives annually. More disturbing is the fact that clinically detectable alcoholic liver disease is beginning to be recognized in adolescents who are identified as having an alcohol use problem in their schools and are referred to our alcohol research program.

Finally, it should be pointed out that cigarette smoking and drug abuse other than alcohol are all dwarfed by the magnitude of the alcohol abuse problem in the United States. In this regard, 95,000 deaths related to alcoholism were estimated to have occurred in 1990. These deaths can be converted into 2.7 million person years lost annually as a result of alcohol abuse at an estimated cost of $24 billion to the economy. The total cost including direct and indirect costs of alcohol abuse is estimated to be between $90 and $116 billion.

PREPARED STATEMENT

Clearly, now is the time to redirect our national priorities and turn the attention of the Nation and its Government to addressing the problems of alcohol abuse and alcoholism. It is for this purpose alone that I am here to persuade you to increase the funding for the National Institutes of Alcoholism and Alcohol Abuse to a level commensurate with its importance. Specifically, I would like to recommend that the 1992 budget for the NIAAA be $205 million. Thank you very much for your attention.

[The statement follows:]

STATEMENT OF DAVID H. VAN THIEL

Mr Chairman and members of the subcommittee; I thank you for the opportunity to appear before you today and to present testimony concerning the issues of alcohol abuse, alcohol research and its funding. My name is David Van Thiel. I am the current president of the Research Society on Alcoholism. I am also the co-scientific director of the Alcohol Research Center at the University of Pittsburgh School of Medicine. Finally, I am the Medical Director of the Transplantation program at the University of Pittsburgh.

As the President of the Research Society on Alcoholism, I represent the large body of basic scientists and psychosocial scientists who are investigating means to identify and treat alcohol abusers and alcoholics as well as prevent both of these important problems.

As the Co-scientific Director of the Alcohol Research Center, I am actively involved in directing, coordinating and the performing of alcohol-related research that relates to the problem of adolescent alcohol abuse. Specifically, the Alcohol Research Center is interested in the physical and psychosocial maturational changes that occur in adolescents and contribute to the initiation and perpetuation of abnormal

use or abuse of alcoholic beverages by the unique population of individuals between ages 10 and 16 years of age.

It must be as obvious to you, as it is to us in Pittsburgh, that any attempt to modify the use and acceptance of alcoholic beverages by adolescents may have profound effects upon both their physical and psychosocial development as well as upon their continued use of alcoholic beverages. In this regard, it is important to note that suicide and accidental death are the two major causes of death among adolescents and that alcohol abuse is estimated to be involved in 30 percent of all suicides and accidental deaths in the general population. The rates for both are probably higher in adolescents than in other age groups. In 1989, motor vehicle crashes' accounted for more than 45,000 deaths of which half were alcohol related. Alcohol related traffic fatalities are the number one cause of adolescent death. Nearly 4 percent of college students or nearly one-half million individuals drink alcohol daily. Worse yet, when surveyed, currently about two-thirds of our young adults do not appreciate the risks associated with excessive alcohol use. At the level of spending, it is estimated that 4.2 billion dollars are spent each year by college students on alcoholic beverages. Shamefully, this figure is more than what is spent on operating college libraries and college scholarships or fellowships throughout the United States on an annual basis. As for our society at large, it should be noted that 49 percent of all murders, 68 percent of all manslaughters, 52 percent of rapes and sexual assaults, 48 percent of all robberies, 62 percent of assaults and 49 percent of violent crime are perpetrated by individuals who are under the influence of alcohol. Many of whom are either adolescents or young adults.

As the Medical Director of the Transplant Program at the University of Pittsburgh I am aware of the fact that alcohol related cirrhosis is the 9th leading cause of death in the United States and annually takes a toll of ≥ 28,000 lives. More disturbing is the fact that clinically detectable alcoholic liver disease is beginning to be recognized in adolescents who are identified as having an alcohol use problem by their schools. The research programs at the Alcohol Research Center in Pittsburgh are directed at identifying adolescents at high risk for continued alcohol abuse, alcoholic liver disease and early cirrhosis as well as strategies to prevent these unwanted outcomes of adolescent experimentation with alcohol.

An area of research that has been neglected in all fields including the field of alcohol abuse and alcoholism is the effects upon the health of women. What little has been done in this underdeveloped area of research has suggested that additional research into the unique problems or consequences of alcohol abuse in women should provide new and valuable information but at a substantial increase in the cost of the research. This is because biomedical and even psychosocial studies in women require that attention be given to the endocrine status of the subjects under investigation. Women in research settings need to be divided into at least 3 groups: those who are menstruating, those who are past-menopausal and those who have yet to have progressed through puberty. It is because of the additional problems of study design that female subjects present rather than issues of sexual bias, that only a handful of studies using female subjects have been performed.

Finally, it should be noted by you that the problems of cigarette smoking and drug abuse other than ethanol abuse are all dwarfed by the magnitude of the problem of alcohol abuse and alcoholism. In this regard, 95,000 deaths related to alcoholism were estimated to have occurred annually. These deaths can be converted into 2.7 million person years lost annually as a result of alcohol abuse at an estimated cost of 24 billion dollars to the economy. Put another way, the total direct and indirect costs of alcohol abuse and alcoholism in the United States for the year 1990 as estimated to be between 90-116 billion dollars.

I am sure that it must be obvious to all of you that every effort to reduce these costs can only be made based upon data obtained at determining the cause or causes of alcohol abuse and alcoholism as well as directing our efforts at prevention of these problems to those actually at risk for the problem.

Clearly now is the time to redirect our national priorities and turn the attention of the nation and its government to addressing the problems of alcohol abuse and alcoholism. It is for this purpose alone that I am here to persuade you to increase the funding for the National Institute on Alcohol Abuse and Alcoholism to a level commensurate with its importance and one that is well above that currently recommended by the current budget presented by President of the United States.

STATEMENT OF TIN-KAI LI

RECOMMENDATION

The Research Society on Alcoholism urges Congress to appropriate $205 million for alcoholism research and training for fiscal year 1992, an amount which is $33.8 million above last year's level. This amount is necessary to (1) bring NIAAA research funding closer to parity with the recent increases enjoyed by KINK_and NIDA, (2) capitalize on the dramatic research opportunities emerging in this field, and (3) expand the nation's war on its greatest substance abuse problem.

ALCOHOLTHE MOST DAMAGING DRUG

Alcohol is a "gateway drug" which often antedates the use of illicit drugs in the United States. Alcohol abuse and dependence (alcoholism) is a frequent concomitant of cocaine and heroin addiction. It is also, frequently, the terminal substance abuse disorder among users of illicit drugs. It is the single most common disorder among mental and addictive disorders in the United States, affecting 15-20 million Americans, and causing 95,000 deaths in a recent year. Fifty percent of all homicides, 30 percent of suicides, and 30 percent of accidental deaths are attributable to alcohol abuse. Thousand of babies are born each year with physical and mental disabilities associated with fetal alcohol exposure resulting from alcohol abuse and dependence among women. Alcoholism takes a disproportionate toll in poor and minority communities, among African-Americans, Hispanics, and Native Americans. Unlike other addictive disorders, alcoholism impacts on rural communities, as well as cities. It is the principal substance abuse problem in most of the United States. Since 1980, three reports have been prepared by the Institute of Medicine analyzing research opportunities in the alcohol field. One recent report by the Institute of Medicine analyzed the changes in alcoholism treatment in the United States in the 1980's. Over the past decade, research on the treatment of alcohol withdrawal has resulted in the development of new techniques that permit outpatient detoxification in a substantial number of alcoholism patients, as well as shorter hospital stays and fewer complications in patients who require hospitalization. The length of inpatient treatment for rehabilitation has declined, and the use of inpatient rehabilitation facilities is no longer recommended for many patients. These changes in treatment patterns have come about during a period of time when insurance coverage for substance abuse treatment has become more common. Research findings that have highlighted equivalent efficacy of treatment using less costly ambulatory approaches have resulted in substantial cost savings.

GENETICS

Studies of family histories of alcoholic patients, twin studies, adoptee studies, and other approaches have confirmed the familial and genetic risk of developing alcohol dependence. Research currently supported by NIAAA should help to identify specific, heritable, biological characteristics that may be associated with the risk of alcoholism in families. For example, researchers have identified specific genetic factors in oriental families that are associated with reduced risk for the development of alcohol dependence. Alcohol-related medical consequences such as cirrhosis of the liver, alcoholic dementia, alcoholic heart disease, fetal alcohol syndrome, and other organ-related pathologies contribute substantially to the very high cost of health care among alcoholic patients. These alcohol-related pathologies, such as alcoholic cardiomyopathy, pancreatitis, and certain cancers associated with alcohol use, are not distributed equally throughout the alcoholic population. Rather, these disorders are influenced by underlying genetic factors in association with exposure to high levels of alcohol. The research capability now exists to search for the genes that underlie the biochemical and physiological basis for vulnerability to these alcohol-related disorders.

Recent research has indicated that although fetal alcohol syndrome (FAS) affects every ethnic group in the population, there is a higher prevalence of this disorder among African-Americans, at similar levels of alcohol consumption. This suggests that a factor present in this population may be responsible for the increased risk of FAS. An early finding that some African-Americans possess a variant of one of the alcohol enzymes, alcohol dehydrogenase, has raised the possibility that this enzyme (or another) might be linked to increased susceptibility to FAS. Recent research also suggests a genetic link in liver cirrhosis among some alcoholics. Individuals who are at heightened risk for alcoholic cirrhosis may have a unique variant on one of the collagen genes. Collagen is a protein needed for proper liver function,

but there is pathological collagen accumulation in cirrhosis of the liver. Further genetic research will provide knowledge on this issue.

As in research on other chronic, life-threatening disorders (eg: cancer) the organrelated pathologies associated with alcoholism require consideration of both genetic and environmental factors associated with risk and pathological mechanisms. The recent IOM reports highlight the high health care costs associated with alcohol-related pathologies. Between 20 and 50 percent of patients hospitalized on medical or surgical units of general hospitals suffer from alcohol-related disorders. Genetic research on organ-related pathologies will lead to more effective methods of prevention, early identification, and treatment with real consequent reductions in health care costs currently associated with these disorders.

MEDICATION DEVELOPMENT

The IOM report on Prevention and Treatment of Alcohol Problems (1989) highlighted prospects for studies of patient/treatment matching, which were recently launched by NIAAA. The report also noted the need to develop new medication to facilitate alcohol rehabilitation for the significant number of patients who presently fail to respond adequately to traditional treatments. The previous IOM report on Causes and Consequences of Alcohol Problems (1987) highlighted the opportunities for research on the neuropharmacology of ethanol. Over the past decade, our knowledge about the brain processes that underlie alcohol addiction has increased tremendously, offering possible targets for new medication. Among the targets for pharmacological treatment are: the intense hunger (or craving for alcohol experienced by alcoholic patients; the cognitive (intellectual) impairments, which-diminish a patient's potential to benefit from traditional treatments; and the protracted withdrawal syndrome-a prolonged state of physiological discomfort, which may contribute to the high rate of relapse during the early months of sobriety. Promising early results with two relatively new classes of drugs (serotonin uptake inhibitors and narcotic antagonists) suggests that it may be possible to attenuate the appetite for alcohol, particularly when these drugs are combined with non-pharmacological treatments. Other researchers have been examining the best way to combine traditional pharmacotherapies such as disulfiram (Antabuse) with behavioral treatments designed to improve medication compliance. As new drugs are developed that enhance cognitive (intellectual) performance (nootropic agents), alcohol researchers will be interested in studying these agents in the treatment of alcohol-related brain diseases including dementia, alcoholic amnestic disorder, as well as the shorter term residual intellectual impairments in memory and judgment that complicate rehabilitation in many patients.

BRAIN IMAGING

The 1987 IOM report also highlighted the importance of new technologies for imaging the living brain and its relationship to the acute and chronic effects of alcohol. These techniques provide a window to view the brain structure, biochemistry, and physiology, and can be used to identify individuals at high risk for alcoholism. Indeed, an electrophysiological abnormality in sons of alcoholics has proven to be one of the more interesting markers in studies of sons of alcoholics. Newer technologies may permit greater specificity that will facilitate early identification of individuals at risk, and more effective approaches to prevention. The techniques may also shed light on mechanism which contribute to risk. Brain imaging techniques, such as Positron Emission Tomography, permit researchers to define the involvement of specific neurotransmitter systems in alcohol-related brain disorders. All of the new techniques of brain imaging-including PET, Single Photon Emission Computerized Tomography (SPECT), Magnetic Resonance Imaging (MRI), Magnetic Resonance Spectroscopy (MRS), as well as advanced methods of instrumentation for electrophysiological methods-hold tremendous promise for alcohol research. In particular, these methods should help to identify more specific risk factors related to brain function, as well as more specific pathological mechanism associated with the development of alcohol abuse and alcohol dependence, that should lead to improved prevention (as well as the development of more effective treatment, including pharmacotherapy).

CONCLUSION

In summary, the costs of alcohol abuse and alcoholism far outweigh the costs of all other addictive disorders combined. Yet, the investment in alcohol research relative to the health care costs associated with this disorder have been very small. IOM reports have clearly defined the research opportunities. On a small research

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